It is the aim of the proposed research to develop a large-scale purification for human sphingomyelinase. Currently available procedures are incapable of producing sufficient enzyme for antibody production. The development of a commercial diagnostic kit for the in utero identification of variants of Niemann-Pick disease by an analogous method to that used by Ginns, et al (Proc. Nat. Acad. Sci. USA 79 5607-5610) for variants of Gaucher's disease, depends on the availability of large amounts of homogeneous sphingomyelinase. Based on experience derived from the large-scale purification of two related enzymes, Glucocerebrosidase and Ceramidetrihexosidase, a two stage purification is proposed. In the first phase extraction, volume reduction and moderate purification will be realized using precipitations, organic extractions and batch chromatography. A fine purification will follow in which column chromatography will be utilized to yield homogeneous enzyme.